LymphomaPhase 1/2NCT00299182
Study of AMG 531 to Evaluate the Safety & Efficacy in Patients With Non-Hodgkin's Lymphoma
A Phase 1/2 study testing AMG 531, Rituximab and Cyclophosphamide in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the highest safe dose of AMG 531 that can be given to treat thrombocytopenia (low platelet counts) in patients who have received chemotherapy. Researchers will also look at the safety and effectiveness of AMG 531. Primary Objectives: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- AMG 531, Rituximab and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to Apr 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a diagnosis of previously untreated aggressive non-Hodgkin's lymphoma, including patients with mantle cell lymphoma, who will be or are receiving treatment with R-HyperCVAD and R-Ara-C/MTX. Patients in whom Rituximab is not used, due to contraindication, will be eligible. Patients whose therapy was switched to (R)Hyper-CVAD after initial treatment with (R)CHOP, because of aggressive disease will also be eligible for the study.
- Patients age >/= 18 years.
- Karnofsky Performance Scale >/= 70.
- Adequate hematologic (ANC >/= 1000/mm(3), platelet count >/= 100,000/mm(3) and Hgb >/= 8gm/dL), renal (serum creatinine < 2mg/dL), and hepatic functions (total bilirubin </= 2 times, serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) </= 3 times the upper limit of the respective normal range).
- Patients (male and female) with childbearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) must use adequate birth control.
- Institutional Review Board (IRB)-approved signed informed consent.
Who cannot join
- Pregnant or lactating women.
- History of Central Nervous System (CNS) involvement.
- Co-morbid medical or psychiatric illnesses that preclude treatment with intense dose chemotherapy.
- Patients with history of deep vein thrombosis (DVT) or pulmonary embolus.
- History of any platelet disorders including Idiopathic thrombocytopenic purpura (ITP), Thrombotic thrombocytopenic purpura (TTP) or bleeding disorders.
- Prior surgery or Radiation Therapy (RT) within 2 weeks of study entry.
- Patients with significant cardiac disease (New York Heart Association (NYHA) Class III or IV), dysrrhythmia, or recent history of myocardial ischemia (MI) or ischemia, transient ischemic attack or cerebrovascular accident (CVA) within the previous 6 months of study entry.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1/2 Study of AMG 531 to Evaluate the Safety, Efficacy, and Pharmacokinetics in Patients With Aggressive Non-Hodgkin's Lymphoma Receiving R-HyperCVAD Alternating With R-Ara-C/MTX
The goal of this clinical research study is to find the highest safe dose of AMG 531 that can be given to treat thrombocytopenia (low platelet counts) in patients who have received chemotherapy. Researchers will also look at the safety and effectiveness of AMG 531.
Primary Objectives:
Read more
- To determine the clinical safety and tolerability of AMG 531 administered following chemotherapy (R-HyperCVAD alternating with R-Ara-C/MTX) in patients with non-Hodgkin's lymphoma.
- To determine an optimal biologic dose (OBD) of AMG 531 in patients receiving R-HyperCVAD and R-Ara-C/MTX.
- To evaluate the effects of AMG 531 on the degree and duration of thrombocytopenia and platelet recovery following chemotherapy(chemo).
Secondary Objectives:
- To evaluate limited pharmacokinetics of AMG 531 administered by S.C. route with chemotherapy.
Read the detailed description
Platelets are cells that help make the blood clot. A decrease in platelets can cause bleeding, which may prevent or delay a patient from receiving chemotherapy. R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and R-Ara-C/MTX (rituximab, cytarabine, and methotrexate) are two chemotherapy regimens that are known to increase the risk of lower platelet counts. Researchers want to find out if AMG 531 can lower the risk and severity of this side effect. AMG 531 is a protein that stimulates platelet production.
Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam, including measurement of vital signs (temperature, pulse, breathing rate, and blood pressure). You will have blood collected (about 3 teaspoons) for routine tests. Radiologic tests such as CT or MRI scans will be done as needed. Women who are able to have children must have a negative blood pregnancy test.
You will also have about 1 teaspoon of blood drawn to see if the you have antibodies to the study drug.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of four treatment groups. These 4 groups will also be split into 2 separate subgroups (Arm A and Arm B). Participants in Arm A will either receive AMG 531 or placebo on Day -5 (5 days before chemotherapy starts) and Day 5 (5 days after chemotherapy starts). A placebo is a substance that looks like the study drug but which has no active ingredients. Every 2 out of 3 participants in Arm A will receive AMG 531. One out of every 3 participants in Arm A will receive placebo.
Participants in Arm B will receive either AMG 531 or placebo on Day 5 and 7. Every 2 out of 3 participants in Arm B will receive AMG 531. One out of every 3 participants in Arm B will receive placebo. The dose of AMG 531 that participants in both Arms A and B receive will depend on when they enroll on the study. There are 3 different dose levels of AMG 531 being studied. Each new group of participants will receive a higher dose than the previous group.
All participants will receive treatment with R-HyperCVAD and R-Ara-C/MTX chemotherapy by vein in alternating cycles. In Cycle 1, all participants will receive R-HyperCVAD by itself. Each cycle is 3 weeks long.
Three (3) weeks later, in Cycle 2, all participants will receive either AMG 531 or placebo following R-Ara-C/MTX. The AMG 531/placebo will be given as an injection under the skin on Days -5 and 5 (Arm A) or on Days 5 and 7 (Arm B). After 2 cycles of treatment, based on response of the disease and tolerance to the treatment, all participants may be able to receive up to 4 more cycles of chemotherapy followed by AMG 531. For Cycles 3-6, you will follow the same schedule of therapy as in the first 2 cycles. The dose of AMG 531 may be increased at one time point during the study based on the response of the platelet counts.
Blood (about 1 teaspoon) will be collected for the evaluation of anti-AMG 531 antibody status at the end of Cycles 2 and 4. You will be taken off the study if your disease gets worse or intolerable side effects occur. The number of blood tests drawn will depend on your clinical condition. These samples (about 1 teaspoon each) will be taken at least 2 times a week and as often as once a day during anticipated periods of low blood cell counts.
At the end of the study, you will have an interim medical history and physical exam, including measurement of vital signs. You will have blood (about 1 teaspoon) drawn for routine end-of-study analysis. Blood (about 1 teaspoon) will also be collected for the evaluation of anti-AMG 531 antibody status.
This is an investigational study. R-HyperCVAD and R-Ara-C/MTX are commercially available chemotherapy drugs. AMG 531 is not FDA approved or commercially available. At this time, AMG 531 is being used in this study for research purposes only. About 36 evaluable patients (maximum of 50 patients) will take part in this study. All will be enrolled at University of Texas (UT) M. D. Anderson.
- Conditions
- Lymphoma
- Being tested
- AMG 531, Rituximab, Cyclophosphamide, Vincristine, Doxorubicin
- Keywords
- Non-Hodgkin's Lymphoma, Lymphoma, Mantle Cell Lymphoma, AMG 531, Romiplostim, Placebo, R-HyperCVAD, R-Ara-C/MTX, Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin, Methotrexate, Rituximab, Vincristine, Decadron, Neosar, AD, Hydroxydaunomycin hydrocholoride, Ara-C
- Medical subject headings
- Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 531Drug
Also called Romiplostim
Arm A: AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days -5 and 5 (pre and post chemotherapy dose) beginning with Cycle 2; OR, Arm A: AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2.
RituximabDrug
Also called Rituxan
375 mg/m^2 by vein over 4-6 hour infusion day 1, each cycle.
CyclophosphamideDrug
Also called Cytoxan, Neosar
300 mg/m^2 by vein over 3 hours every 12 hours for 6 doses (days 2-4), Cycles 1,3, \& 5.
VincristineDrug
1.4 mg/m^2/dose (maximum 2 mg) by vein over 15 minutes Days 5 and 12, Cycles 1,3,\& 5.
DoxorubicinDrug
Also called AD, Hydroxydaunomycin hydrocholoride
50 mg/m^2/dose by vein over 15 minutes on Day 5 or by continuous infusion over 24-48 hours (days 5-6), Cycles 1,3,\& 5.
DexamethasoneDrug
Also called Decadron
40 mg/day by mouth or by vein days 2-5 and 12-15, Cycles 1,3,\& 5.
MethotrexateDrug
200 mg/m^2 by vein over 2 hours followed by 800 mg/m^2 over 22 hours Day 2, Cycles 2, 4 \& 6.
CytarabineDrug
Also called Ara-C, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride
3 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 \& 4; OR,1 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 \& 4 for patients > 60 years and for patients with serum creatinine > 1.5 mg/dL; Cycles 2,4,\& 6.
PlaceboDrug
Arm A: Placebo - subcutaneous injection administered on days -5 and 5 (pre and post chemotherapy dose) beginning with Cycle 2; OR, Arm B: Placebo - subcutaneous injection administered on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2.
| Study group | Role | What they receive |
|---|---|---|
| 1 mcg/ kg AMG531 Pre & Post Chemotherapy | Experimental | Cycle 1, Chemotherapy (R-HyperCVAD) alone.
Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 1 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A)
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. Receives: Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine |
| 3 mcg/ kg AMG531 Pre & Post Chemotherapy | Experimental | Cycle 1, Chemotherapy (R-HyperCVAD) alone.
Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 3 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A)
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. Receives: Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine |
| 10 mcg/ kg AMG531 Pre & Post Chemotherapy | Experimental | Cycle 1, Chemotherapy (R-HyperCVAD) alone.
Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 10 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A)
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. Receives: Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine |
| Placebo (Arm A & Arm B) with Chemotherapy | Placebo comparator | Placebo Pre and Post (Arm A), or Post (Arm B) Chemotherapy
Cycle 1, Chemotherapy (R-HyperCVAD) alone.
Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by placebo subcutaneously on days -5 and 5 (Arm A) or days 5 and 7 (Arm B)
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. Receives: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine; Drug: Placebo |
| 1 mcg/ kg AMG531 Post Chemotherapy | Experimental | Cycle 1, Chemotherapy (R-HyperCVAD) alone.
Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 1 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B)
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. Receives: Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine |
| 3 mcg/ kg AMG531 Post Chemotherapy | Experimental | Cycle 1, Chemotherapy (R-HyperCVAD) alone.
Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 3 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B)
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. Receives: Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine |
| 10 mcg/ kg AMG531 Post Chemotherapy | Experimental | Cycle 1, Chemotherapy (R-HyperCVAD) alone.
Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 10 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B)
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. Receives: Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet (PLT) Nadir
Blood counts were performed at least two times a week and when clinically indicated during the study and daily when PLT count is < 50K/μL until recovery (two consecutive counts showing upward trend). The optimal biologic dose was defined as the dose of AMG 531 at which the greatest proportion of patients avoided grade 4 thrombocytopenia (Platelet nadir < 25K/μL) in the absence of platelet transfusion in the blinded study cycle.
Measured: Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)
Days Platelets Count of < 100K/μL
The optimal biologic dose was defined as the dose of AMG 531 at which the greatest proportion of patients avoided grade 4 thrombocytopenia (Platelet nadir < 25K/μL) in the absence of platelet transfusion in the blinded study cycle.
Measured: Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2006 (estimated)
- Study startMar 2006
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- Saroj Vadhan-Raj, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00299182
- Sponsor's protocol ID
- 2005-0146
- Status last verified
- Aug 2021
- First submitted
- 3 Mar 2006
- Last updated
- 21 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study of AMG 531 to Evaluate the Safety, Efficacy, and Pharmacokinetics in Patients With Aggressive Non-Hodgkin's Lymphoma Receiving R-HyperCVAD Alternating With R-Ara-C/MTX
- ClinicalTrials.gov ID
- NCT00299182
- Acronym / sponsor ID
- 2005-0146
- Conditions
- Lymphoma
- Keywords
- Non-Hodgkin's Lymphoma, Lymphoma, Mantle Cell Lymphoma, AMG 531, Romiplostim, Placebo, R-HyperCVAD, R-Ara-C/MTX
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Mar 2006
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 6 Mar 2006 (estimated)
- Results
- Posted 21 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to find the highest safe dose of AMG 531 that can be given to treat thrombocytopenia (low platelet counts) in patients who have received chemotherapy. Researchers will also look at the safety and effectiveness of AMG 531.
Primary Objectives:
- To determine the clinical safety and tolerability of AMG 531 administered following chemotherapy (R-HyperCVAD alternating with R-Ara-C/MTX) in patients with non-Hodgkin's lymphoma.
- To determine an optimal biologic dose (OBD) of AMG 531 in patients receiving R-HyperCVAD and R-Ara-C/MTX.
- To evaluate the effects of AMG 531 on the degree and duration of thrombocytopenia and platelet recovery following chemotherapy(chemo).
Secondary Objectives:
- To evaluate limited pharmacokinetics of AMG 531 administered by S.C. route with chemotherapy.
Detailed description
Platelets are cells that help make the blood clot. A decrease in platelets can cause bleeding, which may prevent or delay a patient from receiving chemotherapy. R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and R-Ara-C/MTX (rituximab, cytarabine, and methotrexate) are two chemotherapy regimens that are known to increase the risk of lower platelet counts. Researchers want to find out if AMG 531 can lower the risk and severity of this side effect. AMG 531 is a protein that stimulates platelet production.
Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam, including measurement of vital signs (temperature, pulse, breathing rate, and blood pressure). You will have blood collected (about 3 teaspoons) for routine tests. Radiologic tests such as CT or MRI scans will be done as needed. Women who are able to have children must have a negative blood pregnancy test.
You will also have about 1 teaspoon of blood drawn to see if the you have antibodies to the study drug.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of four treatment groups. These 4 groups will also be split into 2 separate subgroups (Arm A and Arm B). Participants in Arm A will either receive AMG 531 or placebo on Day -5 (5 days before chemotherapy starts) and Day 5 (5 days after chemotherapy starts). A placebo is a substance that looks like the study drug but which has no active ingredients. Every 2 out of 3 participants in Arm A will receive AMG 531. One out of every 3 participants in Arm A will receive placebo.
Participants in Arm B will receive either AMG 531 or placebo on Day 5 and 7. Every 2 out of 3 participants in Arm B will receive AMG 531. One out of every 3 participants in Arm B will receive placebo. The dose of AMG 531 that participants in both Arms A and B receive will depend on when they enroll on the study. There are 3 different dose levels of AMG 531 being studied. Each new group of participants will receive a higher dose than the previous group.
All participants will receive treatment with R-HyperCVAD and R-Ara-C/MTX chemotherapy by vein in alternating cycles. In Cycle 1, all participants will receive R-HyperCVAD by itself. Each cycle is 3 weeks long.
Three (3) weeks later, in Cycle 2, all participants will receive either AMG 531 or placebo following R-Ara-C/MTX. The AMG 531/placebo will be given as an injection under the skin on Days -5 and 5 (Arm A) or on Days 5 and 7 (Arm B). After 2 cycles of treatment, based on response of the disease and tolerance to the treatment, all participants may be able to receive up to 4 more cycles of chemotherapy followed by AMG 531. For Cycles 3-6, you will follow the same schedule of therapy as in the first 2 cycles. The dose of AMG 531 may be increased at one time point during the study based on the response of the platelet counts.
Blood (about 1 teaspoon) will be collected for the evaluation of anti-AMG 531 antibody status at the end of Cycles 2 and 4. You will be taken off the study if your disease gets worse or intolerable side effects occur. The number of blood tests drawn will depend on your clinical condition. These samples (about 1 teaspoon each) will be taken at least 2 times a week and as often as once a day during anticipated periods of low blood cell counts.
At the end of the study, you will have an interim medical history and physical exam, including measurement of vital signs. You will have blood (about 1 teaspoon) drawn for routine end-of-study analysis. Blood (about 1 teaspoon) will also be collected for the evaluation of anti-AMG 531 antibody status.
This is an investigational study. R-HyperCVAD and R-Ara-C/MTX are commercially available chemotherapy drugs. AMG 531 is not FDA approved or commercially available. At this time, AMG 531 is being used in this study for research purposes only. About 36 evaluable patients (maximum of 50 patients) will take part in this study. All will be enrolled at University of Texas (UT) M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 1 mcg/ kg AMG531 Pre & Post Chemotherapy | Experimental | Drug: AMG 531, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin, Drug: Dexamethasone, Drug: Methotrexate, Drug: CytarabineCycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 1 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. |
| 3 mcg/ kg AMG531 Pre & Post Chemotherapy | Experimental | Drug: AMG 531, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin, Drug: Dexamethasone, Drug: Methotrexate, Drug: CytarabineCycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 3 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. |
| 10 mcg/ kg AMG531 Pre & Post Chemotherapy | Experimental | Drug: AMG 531, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin, Drug: Dexamethasone, Drug: Methotrexate, Drug: CytarabineCycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 10 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. |
| Placebo (Arm A & Arm B) with Chemotherapy | Placebo comparator | Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin, Drug: Dexamethasone, Drug: Methotrexate, Drug: Cytarabine, Drug: PlaceboPlacebo Pre and Post (Arm A), or Post (Arm B) Chemotherapy Cycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by placebo subcutaneously on days -5 and 5 (Arm A) or days 5 and 7 (Arm B) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. |
| 1 mcg/ kg AMG531 Post Chemotherapy | Experimental | Drug: AMG 531, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin, Drug: Dexamethasone, Drug: Methotrexate, Drug: CytarabineCycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 1 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. |
| 3 mcg/ kg AMG531 Post Chemotherapy | Experimental | Drug: AMG 531, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin, Drug: Dexamethasone, Drug: Methotrexate, Drug: CytarabineCycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 3 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. |
| 10 mcg/ kg AMG531 Post Chemotherapy | Experimental | Drug: AMG 531, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin, Drug: Dexamethasone, Drug: Methotrexate, Drug: CytarabineCycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 10 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m^2; plus Cyclophosphamide 300 mg/m^2, Vincristine 1.4 mg/m^2, Doxorubicin (Adriamycin) 50 mg/m^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m^2; and, R-Ara-C/MTX is Rituximab 375 mg/m^2, Cytarabine 3 g/m^2 and Methotrexate 200 mg/m^2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with a diagnosis of previously untreated aggressive non-Hodgkin's lymphoma, including patients with mantle cell lymphoma, who will be or are receiving treatment with R-HyperCVAD and R-Ara-C/MTX. Patients in whom Rituximab is not used, due to contraindication, will be eligible. Patients whose therapy was switched to (R)Hyper-CVAD after initial treatment with (R)CHOP, because of aggressive disease will also be eligible for the study.
- Patients age >/= 18 years.
- Karnofsky Performance Scale >/= 70.
- Adequate hematologic (ANC >/= 1000/mm(3), platelet count >/= 100,000/mm(3) and Hgb >/= 8gm/dL), renal (serum creatinine < 2mg/dL), and hepatic functions (total bilirubin </= 2 times, serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) </= 3 times the upper limit of the respective normal range).
- Patients (male and female) with childbearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) must use adequate birth control.
Key exclusion criteria (7 listed)
- Pregnant or lactating women.
- History of Central Nervous System (CNS) involvement.
- Co-morbid medical or psychiatric illnesses that preclude treatment with intense dose chemotherapy.
- Patients with history of deep vein thrombosis (DVT) or pulmonary embolus.
- History of any platelet disorders including Idiopathic thrombocytopenic purpura (ITP), Thrombotic thrombocytopenic purpura (TTP) or bleeding disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 531Also: RomiplostimArm A: AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days -5 and 5 (pre and post chemotherapy dose) beginning with Cycle 2; OR, Arm A: AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2. | Drug | 1 mcg/ kg AMG531 Post Chemotherapy, 1 mcg/ kg AMG531 Pre & Post Chemotherapy, 10 mcg/ kg AMG531 Post Chemotherapy, 10 mcg/ kg AMG531 Pre & Post Chemotherapy, 3 mcg/ kg AMG531 Post Chemotherapy, 3 mcg/ kg AMG531 Pre & Post Chemotherapy |
| RituximabAlso: Rituxan375 mg/m^2 by vein over 4-6 hour infusion day 1, each cycle. | Drug | 1 mcg/ kg AMG531 Post Chemotherapy, 1 mcg/ kg AMG531 Pre & Post Chemotherapy, 10 mcg/ kg AMG531 Post Chemotherapy, 10 mcg/ kg AMG531 Pre & Post Chemotherapy, 3 mcg/ kg AMG531 Post Chemotherapy, 3 mcg/ kg AMG531 Pre & Post Chemotherapy, Placebo (Arm A & Arm B) with Chemotherapy |
| CyclophosphamideAlso: Cytoxan, Neosar300 mg/m^2 by vein over 3 hours every 12 hours for 6 doses (days 2-4), Cycles 1,3, \& 5. | Drug | 1 mcg/ kg AMG531 Post Chemotherapy, 1 mcg/ kg AMG531 Pre & Post Chemotherapy, 10 mcg/ kg AMG531 Post Chemotherapy, 10 mcg/ kg AMG531 Pre & Post Chemotherapy, 3 mcg/ kg AMG531 Post Chemotherapy, 3 mcg/ kg AMG531 Pre & Post Chemotherapy, Placebo (Arm A & Arm B) with Chemotherapy |
| Vincristine1.4 mg/m^2/dose (maximum 2 mg) by vein over 15 minutes Days 5 and 12, Cycles 1,3,\& 5. | Drug | 1 mcg/ kg AMG531 Post Chemotherapy, 1 mcg/ kg AMG531 Pre & Post Chemotherapy, 10 mcg/ kg AMG531 Post Chemotherapy, 10 mcg/ kg AMG531 Pre & Post Chemotherapy, 3 mcg/ kg AMG531 Post Chemotherapy, 3 mcg/ kg AMG531 Pre & Post Chemotherapy, Placebo (Arm A & Arm B) with Chemotherapy |
| DoxorubicinAlso: AD, Hydroxydaunomycin hydrocholoride50 mg/m^2/dose by vein over 15 minutes on Day 5 or by continuous infusion over 24-48 hours (days 5-6), Cycles 1,3,\& 5. | Drug | 1 mcg/ kg AMG531 Post Chemotherapy, 1 mcg/ kg AMG531 Pre & Post Chemotherapy, 10 mcg/ kg AMG531 Post Chemotherapy, 10 mcg/ kg AMG531 Pre & Post Chemotherapy, 3 mcg/ kg AMG531 Post Chemotherapy, 3 mcg/ kg AMG531 Pre & Post Chemotherapy, Placebo (Arm A & Arm B) with Chemotherapy |
| DexamethasoneAlso: Decadron40 mg/day by mouth or by vein days 2-5 and 12-15, Cycles 1,3,\& 5. | Drug | 1 mcg/ kg AMG531 Post Chemotherapy, 1 mcg/ kg AMG531 Pre & Post Chemotherapy, 10 mcg/ kg AMG531 Post Chemotherapy, 10 mcg/ kg AMG531 Pre & Post Chemotherapy, 3 mcg/ kg AMG531 Post Chemotherapy, 3 mcg/ kg AMG531 Pre & Post Chemotherapy, Placebo (Arm A & Arm B) with Chemotherapy |
| Methotrexate200 mg/m^2 by vein over 2 hours followed by 800 mg/m^2 over 22 hours Day 2, Cycles 2, 4 \& 6. | Drug | 1 mcg/ kg AMG531 Post Chemotherapy, 1 mcg/ kg AMG531 Pre & Post Chemotherapy, 10 mcg/ kg AMG531 Post Chemotherapy, 10 mcg/ kg AMG531 Pre & Post Chemotherapy, 3 mcg/ kg AMG531 Post Chemotherapy, 3 mcg/ kg AMG531 Pre & Post Chemotherapy, Placebo (Arm A & Arm B) with Chemotherapy |
| CytarabineAlso: Ara-C, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride3 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 \& 4; OR,1 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 \& 4 for patients > 60 years and for patients with serum creatinine > 1.5 mg/dL; Cycles 2,4,\& 6. | Drug | 1 mcg/ kg AMG531 Post Chemotherapy, 1 mcg/ kg AMG531 Pre & Post Chemotherapy, 10 mcg/ kg AMG531 Post Chemotherapy, 10 mcg/ kg AMG531 Pre & Post Chemotherapy, 3 mcg/ kg AMG531 Post Chemotherapy, 3 mcg/ kg AMG531 Pre & Post Chemotherapy, Placebo (Arm A & Arm B) with Chemotherapy |
| PlaceboArm A: Placebo - subcutaneous injection administered on days -5 and 5 (pre and post chemotherapy dose) beginning with Cycle 2; OR, Arm B: Placebo - subcutaneous injection administered on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2. | Drug | Placebo (Arm A & Arm B) with Chemotherapy |
Primary outcome
Platelet (PLT) Nadir
Time frame: Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)
Blood counts were performed at least two times a week and when clinically indicated during the study and daily when PLT count is < 50K/μL until recovery (two consecutive counts showing upward trend). The optimal biologic dose was defined as the dose of AMG 531 at which the greatest proportion of patients avoided grade 4 thrombocytopenia (Platelet nadir < 25K/μL) in the absence of platelet transfusion in the blinded study cycle.
Days Platelets Count of < 100K/μL
Time frame: Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)
The optimal biologic dose was defined as the dose of AMG 531 at which the greatest proportion of patients avoided grade 4 thrombocytopenia (Platelet nadir < 25K/μL) in the absence of platelet transfusion in the blinded study cycle.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center official websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saroj Vadhan-Raj, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AMG 531, Rituximab and Cyclophosphamide in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet (PLT) Nadir (time frame: Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2021.